The purpose of this program is to characterize and explain age associated losses of muscle strength, its relationships to disability and physical activity, to understand the effects of age and gender on the exercise response to exercise, and to examine the phyiological contributions of motor units to strength production. 1. Analyses from the Baltimore Longitudinal Study of Aging In the past year, we have begun to publish data showing genetic contributions of selected genes on muscle strength and hypertrophy. Individuals heterozygotic for a null polymorph of CNTF, a growth factor that directly affects peripheral neurons and muscle, had higher strength levels than individuals without the null polymorph. The increase in strength was associated with greater force generation per unit of muscle mass which has been called muscle quality. The differences were most prominent at relatively fast contraction speeds, suggesting a possible relationship to muscle power. In addition, we found that heterozygotic subjects seem to use smaller motor units to generate higher force levels than homozygotic subjects. This suggests a more efficient use of motor units at higher force levels. A manuscript was published characterizing longitudinal changes in serum testosterone and free testosterone index in BLSA men. We found similar declines in testosterone both cross sectionally and longitudinally. The serum levels were impacted by BMI, alcohol usage, beta blockers, and cancer. The levels of free testosterone (as estimated by the free testosterone index) but not total serum testosterone has an effect on muscle strength independent of muscle mass. To examine the contribution of muscle strength to daily functions, we have compared timed gait to muscle strength around the knee in BLSA women and men aged 20-90. Rapid gait speed was found to increase linearly to a strength of about 200 Nm, with no further changes in speed at higher strength levels. The plateauing of the strength gait speed curve, argues that 200 Nm represents an upper threshold where an excess in physiological function accumulates that does not increase performance. What was particularly revealing was that 10-15% of men fell above this plateau level, while none of the women reached this level. Also, a plateau was found for normal gait speed where 20% of women fell on the plateau, as well as 40% of men. The striking observation is that women are dependent on the strength to gait speed linear relationship to a far greater extent than are men. Age-associated changes in strength should have a greater negative impact on women's gait than on men's gait, particularly at faster speeds. As another measure of functional ability, we are continuing to measure dynamic posturography on BLSA subjects using the same protocol now being used by NASA in testing their astronauts. The data will be compared to the astronaut data to (1) examine the implications of increasing age on potential long term space flight, and (2) document the sequence and magnitude of changes in various elements of the balance system during normal aging. In addition, we will examine the relationship between muscle strength, cardiovascular fitness, leisure time physical activity on balance performance, and the association between balance performance, gait and falls. Analysis was done to examine the sensory-motor adaptive response of 77 year old US Senator John H. Glenn, Jr. to space flight. One of the primary causes of imbalance in the aged is abnormal vestibular function, especially impaired otolith function. The otolith system monitors linear accelerations, including gravity which provides an unambiguous reference to earth vertical. Postural recovery dynamics of returning astronaut crew members after exposure to microgravity have yielded quantitative models of vestibular otolith contributions to postural stability. Senator Glenn&#8217;s pre-flight balance control performances were well above the median for an age-matched control group. Postural recovery dynamics revealed few differences between Senator Glenn&#8217;s neuro-adaptive responses to space flight and those of a group of younger astronauts. We interpret these findings as evidence that increasing age alone does not necessarily impair balance function. A methodological issue was addressed in how to analyze data from computerized dynamic posturography. A probabilistic model was developed to deal with the occurrence of falls during the testing. 2. The Impact of Strength Intervention on Muscle Physiology and Health The contract with the University of Maryland comparing the exercise response in young and old women and men is completed. Currently the data are under analysis, with multiple manuscripts submitted, in press, and published. We found that both young and old subject respond to the one legged exercise training with a 25 to 35% increase in 1RM strength, though the younger subjects showed a significantly greater increase. Subsequently, following 31 weeks of detraining, these strength levels were retained. The findings argue that strength training can have a sustained effect on both young and elderly individuals over a long time period. The strength increases were associated with muscle hypertrophy with 12% increase in the muscle volume of the quadriceps femoris that did not differ by age. Men showed greater hypertrophy than women. Expressing strength (1RM) per unit of muscle (muscle quality) found an increase in the force generated by muscle in all groups in response to strength training. The observation argues that muscle hypetrophy alone does not account for the entire results from a strength training program, and that other factors affect both young and old subjects as well as men and women. We also found that the level of muscle damage from the resistive training did not differ between young and old men with both groups showing about 6-7% damage. Other benefits may arise from strength training programs. Following 24 weeks of total body training, a transient decline was observed in the blood pressure that lasted for up to 48 hours. However, following the 24 weeks of total body training, there were no reductions in plasma fasting glucose levels, but men seemed to blunt their insulin response during oral glucose tolerance test. Resting metabolic rates were found to increased in both young and old subjects, but this primarily resulted from increases in the men. These increases were directly related to changes in fat free mass. Levels of activity as judged by triaxial accelerometer, and by questionnaire did not change. We have now completed a project using electromyostimulation as an alternative to resistive strength training and the use of a pedometer to encourage increased activity in patients with osteoarthritis of the knee. We are working to develop alternative strategies that will give individuals differing strategies to maintain and increase strength. The data are currently being analyzed. 3. Motor Unit Physiology We continue examine age associated changes in the motor unit and the impact on strength in BLSA subjects. At present, not enough subjects have been completed to allow for analysis. In previous work, we had found that product of average motor unit size and firing rate accounts for more than 70% of the variance in force generation in a large sample of subjects. We have examined the relationship between motor unit size, firing rate and the surface EMG signal. The latter is frequently used to assess muscle function in kinesiology. Motor unit size is more critical than firing rate in accounting for the surface signal in the quadriceps femoris.We are currently analyzing data from the exercise intervention done with University of Maryland.